The present invention relates to the field of polymer synthesis. More specifically, in one embodiment the invention provides an improved method and system for synthesizing arrays of diverse polymer sequences. According to a specific aspect of the invention, a method of synthesizing diverse polymer sequences such as peptides or oligonucleotides is provided. The diverse polymer sequences may be used, for example, in screening studies for determination of binding affinity.
Methods of synthesizing desired polymer sequences such as peptide sequences are well known to those of skill in the art. For example, the so-called "Merrifield" solid-phase peptide synthesis has been in common use for several years and is described in Merrifield, J. Am. Chem Soc. (1963) 85:2149-2154, incorporated herein by reference for all purposes. Solid-phase peptide synthesis techniques have been extended to provide for the synthesis of several peptide sequences on, for example, a number of "pins" as described in, for example, Geysen et al., J. Immun. Meth. (1987) 102:259-274, also incorporated herein by reference for all purposes. Methods of synthesizing oligonucleotides are found in, for example, Oligonucleotide Synthesis: A Practical Approach, Gait, ed., IRL Press, Oxford (1984), incorporated herein by reference in its entirety for all purposes.
Such methods and devices have continued to be limited in the number of sequences which can be synthesized in a reasonable amount of time. For example, Geysen et al. report in the above journal that it has taken approximately 3 years to synthesize 200,000 peptide sequences. Such methods have continued to produce fewer peptide sequences for study than are often desired.
Accordingly, improved methods of forming large arrays of peptides, oligonucleotides, and other polymer sequences in a short period of time have been devised.
Of particular note, Pirrung et al., PCT Application No. WO 90/15070 and U.S. application Ser. No. 07/624,120 abandoned in favor of U.S. Ser. No. 08/390,027 filed Feb. 16, 1995, both incorporated herein by reference, disclose methods of forming vast arrays of peptides and other polymer sequences using, for example, light-directed synthesis techniques. See also, Fodor et al., Science (1991) 251:767-777, also incorporated herein by reference for all purposes.
These techniques have met with substantial success. However, in some cases it is desirable to have alternate/additional methods of forming polymer sequences which would not utilize, for example, light as an activator, or which would not utilize light exclusively.